The Impact of Testosterone Therapy in Men on Cardiovascular Risk

In this issue of Mayo Clinic Proceedings, Morgentaler et al1 provide a timely update regarding testosterone therapy in men and cardiovascular risk. This review is important considering the recent controversy claiming increased cardiovascular risk in men receiving testosterone therapy. Morgentaler et al identified 4 studies suggesting that testosterone therapy increases the risk of cardiovascular events, but they also identified more than 100 studies demonstrating that normal testosterone levels (and, accordingly, physiologic replacement of testosterone) provide beneficial effects to men and minimize cardiovascular risk and mortality. They also critically evaluated the 4 positive studies and noted that 2 studies had serious methodology concerns, 1 was a meta-analysis with poor inclusion criteria, and 1 was a placebo-controlled study with too few cardiovascular events to make definitive conclusions.

Morgentaler et al are not alone when it comes to concerns raised about the recent studies reporting adverse cardiovascular effects of testosterone. For example, the methodology concerns in the report by Vigen et al3—one of the reports suggesting harm by testosterone—have been so great that 29 professional societies, including the International Society for Men’s Health, the International Society of Sexual Medicine, and the Sexual Medicine Society of North America, have demanded that the article be retracted.1

In the present review, Morgentaler et al stress that cardiovascular mortality and incident coronary artery disease are associated with lower levels of total testosterone, free testosterone, and bioavailable testosterone. In a study by Ohlsson et al,6 for example, men with serum total testosterone concentration levels of 550 ng/dL or more (ie, the highest quartile) had a 30% lower risk of cardiovascular events than did men in the 3 lower quartiles, even after adjusting for traditional cardiovascular risk factors and excluding men with known baseline cardiovascular disease. At first glance, these are somewhat paradoxical observations considering the recent inquiries by the Food and Drug Administration (FDA), a call for more stringent product labeling, and an outcry in the lay press that testosterone therapy is hazardous.